The role of a humoral mechanism in the natriuresis of volume expansion will be investigated using the isolated perfused dog kidney. The dog will be volume expanded with equilibrated blood and the change in sodium excretion from the isolated kidney measured. Blood will be collected before and after volume expansion, fractionated by gel filtration and assayed for natriuretic activity using the from skin bioassay. After identifying the active fraction, it will be tested for natriburetic activity in the isolated kidney. The effect of organ ablation on volume expansion natriuresis in the isolated kidney will be examined and correlated with the presence or absence of natriuretic activity in plasma using the frog skin bioassay in an attempt to identify the source of the factor. The role of the renin-angiotensin system in mediating autoregulation of renal blood flow and glomerular filtration rate will be evaluated in the isolated kidney. Initially, we will examine the consequence of renin depletion on GFR and RBF autoregulation, single nephron function and the microcirculation using clearance and micropuncture techniques. Subsequently we will investigate the consequences of infusing angiotensin II and converting enzyme inhibitors, anti-renin antibodies and anti-angiotensin I antibodies on the same parameters. The effect of increased renal arterial pressure on proximal tubule sodium transport will be evaluated using non-recollection end-proximal micropuncture technique and correlated with changes in postglomerular capillary hydrostatic and oncotic forces. Alterations in distal tubule sodium transport in response to increased renal arterial pressure will be assessed by the tracer microinjection technique. Changes in free water clearance will be used to define changes in transport along the loop of Henle. Similar techniques will be used to study the relationship between redistribution of RBF from outer to inner cortex and natriuresis in response to renal vasodilators.